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Biomedical subjects

W H Herman

Publications and source records attributed to W H Herman.

At least 19 recordsLinked to original sources
PubMed2006

A Diabetes Outcome Progression Trial (ADOPT): baseline characteristics of Type 2 diabetic patients in North America and Europe.

AIMS: To examine baseline characteristics of patients recruited into ADOPT, a multinational trial comparing three oral glucose-lowering monotherapies. METHODS: Between April 2000 and June 2002, 4360 patients aged 30-75 years with Type 2 diabetes diagnosed for < 3 years and remaining on diet therapy alone with fasting plasma glucose levels (FPG) between 7.0 and 10.0 mmol/l were enrolled by 488 North American and European centres. Medical histories, anthropometric data and laboratory measurements were determined using common methodologies. RESULTS: The mean (SD) age of the patients was 57 (10) years, body mass index 32.2 (6.4) kg/m(2), HbA(1c) 7.4 (0.9)%; 58% were male, 88% Caucasian and 15% smoked. North American Caucasians (NAC) were younger, more obese, and more insulin resistant than European Caucasians (EUC), but had better pancreatic B-cell function. NAC had lower total, low-density lipoprotein- and high-density liporpotein-cholesterol concentrations with higher triglyceride concentrations and were more often on lipid-lowering treatment. They had lower blood pressure levels but were equally likely to be on antihypertensive treatment. Metabolic syndrome was more frequent and microalbuminuria less frequent in NAC. Within North America, NAC had lower HbA(1c) concentrations than Blacks, Hispanics and Asians despite similar or higher FPG and 30-min postchallenge glucose concentrations. CONCLUSIONS: Caucasian North American and European ADOPT patients differ with respect to adiposity, insulin resistance and metabolic syndrome prevalence. North American Blacks, Hispanics and Asians had lower HbA(1c) concentrations than NAC despite similar or higher glucose concentrations. These phenotypic differences may influence the progression of Type 2 diabetes and the response to initial oral glucose-lowering monotherapy.

Adult↗
PubMed2005

A multivariate logistic regression equation to screen for dysglycaemia: development and validation.

AIMS: To develop and validate an empirical equation to screen for dysglycaemia [impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and undiagnosed diabetes]. METHODS: A predictive equation was developed using multiple logistic regression analysis and data collected from 1032 Egyptian subjects with no history of diabetes. The equation incorporated age, sex, body mass index (BMI), post-prandial time (self-reported number of hours since last food or drink other than water), systolic blood pressure, high-density lipoprotein (HDL) cholesterol and random capillary plasma glucose as independent covariates for prediction of dysglycaemia based on fasting plasma glucose (FPG)>or=6.1 mmol/l and/or plasma glucose 2 h after a 75-g oral glucose load (2-h PG)>or=7.8 mmol/l. The equation was validated using a cross-validation procedure. Its performance was also compared with static plasma glucose cut-points for dysglycaemia screening. RESULTS: The predictive equation was calculated with the following logistic regression parameters: P=1+1/(1+e-X)=where X=-8.3390+0.0214 (age in years)+0.6764 (if female)+0.0335 (BMI in kg/m2)+0.0934 (post-prandial time in hours)+0.0141 (systolic blood pressure in mmHg)-0.0110 (HDL in mmol/l)+0.0243 (random capillary plasma glucose in mmol/l). The cut-point for the prediction of dysglycaemia was defined as a probability>or=0.38. The equation's sensitivity was 55%, specificity 90% and positive predictive value (PPV) 65%. When applied to a new sample, the equation's sensitivity was 53%, specificity 89% and PPV 63%. CONCLUSIONS: This multivariate logistic equation improves on currently recommended methods of screening for dysglycaemia and can be easily implemented in a clinical setting using readily available clinical and non-fasting laboratory data and an inexpensive hand-held programmable calculator.

Adult↗
PubMed2004

Glycemia and the quality of well-being in patients with diabetes.

OBJECTIVES: To investigate the cross-sectional relationships among self-reported frequencies of symptomatic hyperglycemia and hypoglycemia, HbA1c, and symptoms in the Quality of Well-Being Self-Administered (QWB-SA), and to examine the associations among these measures of glycemia and health-utility scores. METHODS: The study group included 1522 patients with diabetes who attended University of Michigan Health System clinics. Published studies were reviewed to identify symptoms in the QWB-SA that might be associated with measures of glycemia. Linear-regression analyses were performed to evaluate the strength of the associations among the frequency of self-reported measures of glycemia, QWB-SA symptoms, and QWB-SA-derived health-utility scores. RESULTS: Frequency of hyperglycemic symptoms was associated with 3% of the variance in the QWB-SA-derived health-utility score in type-1 diabetes and with 5% of the variance in type-2 diabetes. Frequency of hypoglycemic symptoms was not associated with the QWB-SA-derived health-utility score in type-1 diabetes but was associated with 1% of the variance in type-2 diabetes. HbAlc levels were not significantly associated with QWB-SA-derived health-utility scores. After controlling for age, gender, and complications, frequency of hyperglycemic symptoms was significantly associated with QWB-SA-derived health-utility scores in type-1 and type-2 diabetes. CONCLUSIONS: Reported frequency of hyperglycemic symptoms is associated with symptoms included in the QWB-SA and with QWB-SA-derived health-utility scores. The QWB-SA may be an appropriate measure to assess the health burden of hyperglycemia.

Adolescent↗
PubMed2001

Does microalbuminuria predict diabetic nephropathy?

OBJECTIVE: To describe risk factors associated with microalbuminuria (MA) in subjects with diabetes, investigate the predictive value of MA as a marker of risk for diabetic nephropathy (DN), and define risk factors associated with the development and progression of MA. RESEARCH DESIGN AND METHODS: We conducted a prospective longitudinal study of 23 diabetic subjects with persistent MA and 209 diabetic subjects without MA who attended diabetes clinics at the University of Michigan Medical Center in 1989 and 1990. Both groups were examined at baseline and after 7 years. At baseline, urinary albumin-to-creatinine ratios were studied in random, first morning, and 24-h urine samples. At follow-up, a 12-h overnight urine sample was collected and analyzed for albumin and creatinine. At baseline, MA was defined by at least two separate urine specimens with albumin-to-creatinine ratios between 30 and 299 microg albumin per milligram of creatinine. RESULTS: MA regressed in 56% of subjects with baseline MA without systematic application of corrective measures and developed in 16% of subjects without baseline MA. The predictive value positive of MA as a marker of risk for DN was 43%, and the predictive value negative was 77%. In the combined cohort, the incidence and progression of MA were significantly associated with poor glycemic control and duration of diabetes between 10 and 14 years. CONCLUSIONS: MA may not be as sensitive and specific a predictor of DN as previously suggested. Other markers of risk for DN are needed for optimal clinical management.

Adolescent↗
PubMed2000

Elevated endothelin-1 in tubular epithelium is associated with renal allograft rejection.

Vascular endothelin-1 (ET-1) levels are elevated in patients with renal allograft rejection, and the mitogenic and pressor actions of ET-1 might contribute to transplant vasculopathy, posttransplantation hypertension, and ischemia-reperfusion injury. In contrast, relatively little is known about tubular expression of ET-1 in acute or chronic rejection of renal allografts. We sought to determine whether tubular ET-1 levels were altered in patients with acute or chronic renal allograft rejection. Immunohistochemical analysis of tubular ET-1 was performed in renal biopsy specimens from 18 patients with acute rejection, 7 patients with chronic rejection, and 5 normal kidneys excised for localized neoplasm. The diagnosis of acute or chronic rejection in each patient was verified and graded using the Banff schema. Renal tubular epithelium from patients with allograft rejection had markedly elevated staining for ET-1 compared with normal kidneys. Tubular ET-1 levels were elevated in 18 of 18 patients with acute rejection and 5 of 7 patients with chronic rejection. Tubular ET-1 staining was graded from 0 to +3 as follows: normal kidneys, 1.2 +/- 0.2; acute rejection, 2.3 +/- 0.4 (P < 0.01); and chronic rejection, 2.2 +/- 0.5 (P < 0.01). ET-1 staining was prominent in both proximal and distal tubules, and we observed abundant ET-1 secretion from proximal tubular epithelium in culture. Moreover, ET-1 activated the c-fos immediate early gene promoter in proximal tubular cells transfected with a c-fos luciferase reporter. We conclude that elevated tubular ET-1 levels are associated with acute and chronic rejection of renal allografts. Our results also suggest distinct pathophysiological roles for the tubular and vascular ET-1 systems in renal allograft rejection.

Adolescent↗
PubMed2000

Ammonium perchlorate contamination of Colorado River drinking water is associated with abnormal thyroid function in newborns in Arizona.

The Colorado River below Lake Mead, which supplies drinking water for approximately 20,000,000 people, is contaminated by ammonium perchlorate. We identified populations who were exposed and unexposed to perchlorate-contaminated drinking water and compared median newborn thyroid-stimulating hormone (TSH) levels after adjusting for age in days at measurement and for race/ethnicity. Median newborn TSH levels in a city whose drinking water supply was 100% perchlorate-contaminated water from the Colorado River below Lake Mead were significantly higher than those in a city totally supplied with non-perchlorate-contaminated drinking water, even after adjusting for factors known or suspected to elevate newborn TSH levels. This ecological study demonstrates a statistically significant association between perchlorate exposure and newborn TSH levels. It suggests that even low-level perchlorate contamination of drinking water may be associated with adverse health effects in neonates and highlights the need for both further study and control of human low-level perchlorate exposure.

Analysis of Variance↗
PubMed2000

Reduced pancreatic polypeptide response to hypoglycemia and amylin response to arginine in subjects with a mutation in the HNF-4alpha/MODY1 gene.

Subjects with the Q268X mutation in the hepatocyte nuclear factor (HNF)-4alpha gene (RW pedigree/maturity-onset diabetes of the young [MODY]-1) have diminished insulin and glucagon secretory responses to arginine. To determine if pancreatic polypeptide (PP) secretion is likewise involved, we studied PP responses to insulin-induced hypoglycemia in 17 RW pedigree members: 6 nondiabetic mutation-negative [ND(-)], 4 nondiabetic mutation-positive [ND(+)], and 7 diabetic mutation-positive [D(+)]. Subjects received 0.08 U/kg body wt human regular insulin as an intravenous bolus to produce moderate self-limited hypoglycemia. PP areas under the curve (PP-AUCs) were compared among groups. With hypoglycemia, the PP-AUC was lower in the D(+) group (14,907 +/- 6,444 pg/ml, P = 0.03) and the ND(+) group (14,622 +/- 6,015 pg/ml, P = 0.04) compared with the ND(-) group (21,120 +/- 4,158 pg/ml). In addition, to determine if the beta-cell secretory defect in response to arginine involves amylin in addition to insulin secretion, we analyzed samples from 17 previously studied RW pedigree subjects. We compared the AUCs during arginine infusions for the 3 groups both at euglycemia and hyperglycemia as well as their C-peptide-to-amylin ratios. The D(+) and ND(+) groups had decreased amylin AUCs during both arginine infusions compared with the ND(-) group, but had similar C-peptide-to-amylin ratios. These results suggest that the HNF-4alpha mutation in the RW/MODY1 pedigree confers a generalized defect in islet cell function involving PP cells in addition to beta- and alpha-cells, and beta-cell impairment involving proportional deficits in insulin and amylin secretion.

Adult↗
PubMed2000

Screening for type 2 diabetes.

Definitive studies of the effectiveness of screening for type 2 diabetes are currently not available. RCTs would be the best means to assess effectiveness, but several barriers prevent these studies from being conducted. Prospective observational studies may characterize some of the benefits of screening by creating screened and unscreened groups for comparison. The availability of better data systems and health services research techniques will facilitate such comparisons. Unfortunately, the interpretation of the results of such studies is extremely problematic. Several screening tests have been evaluated. Risk assessment questionnaires have generally performed poorly as stand-alone tests. Screening with biochemical tests performs better. Venous and capillary glucose measurements may perform more favorably than urinary glucose or HbA(1c) measurements, and measuring postprandial glucose levels may have advantages over measuring fasting levels. However, performance of all screening tests is dependent on the cutoff point selected. Unfortunately, there are no well-defined and validated cutoff points to define positive tests. A two-stage screening test strategy may assist with a more efficient use of resources, although such approaches have not been rigorously tested. The optimal interval for screening is unknown. Even though periodic, targeted, and opportunistic screening within the existing health care system seems to offer the greatest yield and likelihood of appropriate follow-up and treatment, much of the reported experience with screening appears to be episodic poorly targeted community screening outside of the existing health care system. Statistical models have helped to answer some of the key questions concerning areas in which there is lack of empirical data. Current models need to be refined with new clinical and epidemiological information, such as the UKPDS results (200). In addition, future models need to include better information on the natural history of the preclinical phase of diabetes. Data from ongoing clinical trials of screening and treatment of impaired glucose tolerance, such as the Diabetes Prevention Program, may eventually offer more direct evidence for early detection and treatment of asymptomatic hyperglycemia (201). It will be important to use comprehensive cardiovascular disease modules that assess the conjoint influence of glucose and cardiovascular risk factor reduction, information on QOL, and refined economic evaluations using common outcome measures (cost per life-year or QALY gained) (11,178,202-204). Such studies should consider all of the costs associated with a comprehensive screening program, including, at a minimum, the direct costs of screening, diagnostic testing, and care for patients with diabetes detected through screening. Finally, combinations of screening tests and different screening intervals should be evaluated within economic studies to allow selection of the optimal approach within the financial and resource limitations of the health care system.

Blood Glucose↗
PubMed1999

Inhibition of endothelin-converting enzyme attenuates transplant vasculopathy and rejection in rat cardiac allografts.

BACKGROUND: Transplant vasculopathy in kidney and heart allografts is associated with marked elevation of endothelin-1 (ET-1), but a role for ET-1 in the pathogenesis of transplant vasculopathy and chronic rejection has not been established. We, therefore, tested whether inhibition of ET-1-converting enzyme by phosphoramidon (PA) would attenuate rejection in a rat model of chronic cardiac allograft rejection (Lewis [LEW] to F344). METHODS: Donor LEW rats were pretreated 24 hr before transplantation with a bolus injection of vehicle (water) or PA. Twenty- four hour after transplantation, water or PA was continuously administered through an osmotic mini-pump. Plasma ET-1 levels in Fisher 344 (F344) recipients were 0.8+/-0.1 pg/ml in water-treated rats and 0.2+/-0.2 pg/ml (P<0.01) in PA-treated rats, demonstrating that the PA treatment protocol effectively lowered ET-1 biosynthesis. RESULTS: LEW cardiac allografts treated with water survived (i.e., palpable heart beat) for 16.0+/-0.5 days (n=6). Inhibition of ET-1 secretion by PA improved allograft survival to 28.8+/-3.3 days (P<0.01, n=8). An analysis of cardiac arteries demonstrated that PA treatment attenuated transplant vasculopathy. A morphometric scale of neointima formation (0-5) was 1.4+/-0.2 and 3.6+/-0.2 in PA- or water-treated rats, respectively (P<0.01). The percent of luminal occlusion, as measured by microscopic image analysis, was 19+/-6% in PA-treated animals and 38+/-6% (P<0.01) in animals treated with water. PA treatment also reduced infiltration of ED-1-positive monocytes/macrophages into the vascular neointima. CONCLUSIONS: We conclude that, even in the absence of concomitant immunosuppression, inhibition of ET-1 biosynthesis significantly attenuates transplant vasculopathy and improves survival of LEW to F344 cardiac allografts.

Animals↗
PubMed1999

Estimating prevalence of type 1 and type 2 diabetes in a population of African Americans with diabetes mellitus.

The pathogenesis, treatment, and outcomes of type 1 and type 2 diabetes differ. Current surveys derive population-based estimates of diabetes prevalence by type using limited clinical information and applying classification rules developed in white populations. How well these rules perform when deriving similar estimates in African American populations is unknown. For this study, data were collected on a group of African Americans with diabetes who enrolled at the Diabetes Unit of Grady Memorial Hospital in Atlanta, Georgia, from April 16, 1991, to November 1, 1996. The data were used to develop some simple classification rules for African Americans based on a classification tree and a logistic regression model. Sensitivities and specificities, in which fasting C-peptide was used as the gold standard, were determined for these rules and for two current rules developed in mostly white, non-Hispanic populations. Rules that yielded precise (minimum variance unbiased) estimates of the prevalence of type 1 diabetes were preferred. The authors found that a rule based on the logistic regression model was best for estimating type 1 prevalences ranging from 1% to 17%. They concluded that simple classification rules can be used to estimate prevalence of diabetes by type in African American populations and that the optimal rule differs somewhat from the current rules.

Adult↗
PubMed1999

The diagnosis and classification of diabetes mellitus in nonpregnant adults.

This article reviews the definition, diagnosis, and classification of diabetes and focuses on the rationale for and the limitations of the new diagnostic criteria for diabetes adopted by the American Diabetes Association in 1997. It also reviews the impact of the new fasting criterion for diabetes on both the prevalence of diabetes and the phenotype of individuals identified. Finally, it describes the revised classification scheme for diabetes and explains how it simplifies and clarifies some of the confusion created by the previous scheme.

Adult↗
PubMed1999

Renal assessment practices and the effect of nurse case management of health maintenance organization patients with diabetes.

OBJECTIVE: To examine baseline renal screening practices and the effect of nurse case management of patients with diabetes in a group model health maintenance organization (HMO). RESEARCH DESIGN AND METHODS: We performed both 1-year retrospective and 1-year prospective studies of renal assessment practices and ACE inhibitor usage in a cohort of 133 diabetic patients enrolled in a randomized controlled trial of a diabetes nurse case management program in a group model HMO. In accordance with American Diabetes Association recommendations, urine dipstick and quantitative protein and microalbuminuria testing rates were calculated. RESULTS: At baseline, 77% of patients were screened for proteinuria with dipsticks or had quantitative urine testing. Of patients with negative dipstick findings, 30% had appropriate quantitative protein or microalbumin follow-up at baseline. Baseline ACE inhibitor usage was associated with decreased follow-up testing (relative risk = 0.47). Nurse case management was associated with increased quantitative protein or or microalbumin testing and increased follow-up testing (relative risk = 1.65 and 1.60, respectively). CONCLUSIONS: We found a higher degree of adherence to recommendations for renal testing than has been reported previously. Nurse case management intervention further increased renal screening rates. The inverse association between ACE inhibitor usage and microalbumin testing highlights a potentially ambiguous area of current clinical pathways.

Albuminuria↗
PubMed1999

Effect of simvastatin treatment on cardiovascular resource utilization in impaired fasting glucose and diabetes. Findings from the Scandinavian Simvastatin Survival Study.

OBJECTIVE: The Scandinavian Simvastatin Survival Study showed that simvastatin treatment reduced cardiovascular events in hypercholesterolemic subjects with coronary heart disease. The clinical benefits of therapy were similar in all three subgroups: normal fasting glucose (NFG, n = 3,237), impaired fasting glucose (IFG, n = 678), and diabetes (n = 483). This analysis compared the costs of simvastatin treatment with the costs of cardiovascular disease-related hospitalizations in the three subgroups. RESEARCH DESIGN AND METHODS: The cost of simvastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences. The costs of cardiovascular disease-related hospitalizations were determined by actual rates of hospitalization and 1995 MEDSTAT diagnosis-related group costs. RESULTS: Within trial, simvastatin treatment cost approximately $6,000 per patient. Simvastatin treatment reduced cardiovascular disease-related hospitalizations by 23% in NFG (P = 0.001), 30% in IFG (P = 0.015), and 40% in diabetic subjects (P = 0.007) within trial (median follow-up of 5.4 years). Average length of stay was reduced by 2.4 days in diabetic subjects (P = 0.021). Total cardiovascular disease-related hospital days were reduced by 28% (P < 0.001) in NFG, 38% (P = 0.005) in IFG, and 55% (P < 0.001) in diabetic subjects. For NFG subjects, simvastatin reduced the average cost of cardiovascular disease-related hospitalizations by $3,585, which offset 60% of the cost of simvastatin therapy. For IFG subjects, average cardiovascular disease-related hospitalization costs were reduced by $4,478, which offset 74% of the drug cost. For diabetic subjects, there was a net cost savings of $1,801 per subject within trial. CONCLUSIONS: Simvastatin significantly reduced cardiovascular disease-related hospitalizations and total hospital days for all three groups and significantly reduced length of stay for the diabetic group in addition to providing significant clinical benefits. The benefits were greatest in the diabetic group, with estimated cost savings within trial from simvastatin treatment.

Cardiovascular Diseases↗
PubMed1999

Effect of selective screening for gestational diabetes.

OBJECTIVE: To estimate the percentage of pregnant women who would not be screened and the percentage of women with gestational diabetes mellitus (GDM) who would possibly remain undiagnosed if the American Diabetes Association's (ADA's) new selective screening recommendations are used rather than universal screening for GDM. RESEARCH DESIGN AND METHODS: Since 1987, the University of Michigan Health System has performed universal screening for GDM. In 1997, the ADA recommended that women having all four of the following characteristics need not be screened: age < 25 years, not members of an ethnic/racial group with a high prevalence of diabetes, normal body weight, and no family history of diabetes. We studied a random sample of the 25,118 deliveries at the University of Michigan between 1987 and 1997 to determine the prevalence of these four characteristics in our obstetric population. We also studied the prevalence of these four characteristics in 200 women who were diagnosed with GDM in the Endocrine Testing Unit and delivered at the University of Michigan between 1987 and 1997. RESULTS: Approximately 10-11% of women who delivered possessed all four low-risk characteristics and would not have been screened for GDM according to the new ADA recommendations. Only 4% of women (5 of 141) with GDM who delivered and for whom data on all four characteristics were reported possessed all four low-risk characteristics and would not have been screened. CONCLUSIONS: If the new ADA selective screening recommendations are used, few women with GDM will be missed (4%) but approximately 90% of pregnant women will still need to be screened for GDM.

Adult↗
PubMed1999

Impact of maternal nativity on the prevalence of diabetes during pregnancy among U.S. ethnic groups.

OBJECTIVE: This study examines the impact of maternal nativity (birthplace) on the overall prevalence of diabetes during pregnancy and among 15 racial and ethnic groups in the U.S. RESEARCH DESIGN AND METHODS: Birth certificate data for all resident single live births in the U.S. from 1994 to 1996 were used to calculate reported diabetes prevalence during pregnancy and to assess the impact of maternal birthplace outside of the 50 states and Washington, DC, on the risk of diabetes before and after adjustment for differences in maternal age, other sociodemographic characteristics, and late or no initiation of prenatal care overall and for each racial and ethnic group. RESULTS: Mothers born outside of the U.S. are significantly more likely to have diabetes during pregnancy. The impact of maternal nativity on diabetes prevalence is largely explained by the older childbearing age of immigrant mothers. However, adjusted diabetes risk remains elevated for Asian-Indian, non-Hispanic black, Filipino, Puerto Rican, and Central and South American mothers who were born outside the U.S. Conversely, birthplace outside the U.S. significantly reduces diabetes risk for Japanese, Mexican, and Native American women. CONCLUSIONS: Identification, treatment, and follow-up of immigrant mothers with diabetes during pregnancy may require special attention to language and sociocultural barriers to effective care. Systematic surveillance of the prevalence and impact of diabetes during pregnancy for immigrant and nonimmigrant women, particularly in racial and ethnic minority groups, and more detailed studies on the impact of acculturation on diabetes may increase understanding of the epidemiology of diabetes during pregnancy in our increasingly diverse society.

Adult↗